Non Small Cell Lung Cancer Clinical Trial
Official title:
Detection of Circulating Biomarkers of Immunogenic Cell Death After Radiotherapy and Chemotherapy: An Exploratory Study
In this exploratory study, the investigators will investigate if markers (molecular and immunological) of ICD or anti-tumor immunity (exosomal or molecular) can be detected in the serum of patients after high-dose radiotherapy alone or concurrent cisplatin-doublet therapy and radiotherapy. For each patient: withdraw blood at three times during treatment for analysis.
The main aim of anticancer therapies is to exert cytotoxic effects on cancer cells. It
recently emerged that some anticancer therapeutic modalities are capable of inducing a cell
death subroutine called immunogenic cell death (ICD) that can mediate specific, sustained
anticancer immunity. These observations have marked the beginning of intense research into
immunoadjuvant or anticancer immunity inducing "side-effects" associated with anticancer
therapies.
At present, in humans, no ICD-associated predictive biomarkers have been identified, which
hampers the development of immunological strategies. No published data about human biomarkers
for ICD is available.
In vitro, ICD has been found to be associated with the spatiotemporally defined emission of
danger signals such as surface exposed calreticulin (CRT) or heat shock protein 90 (HSP90),
secreted ATP and released TLR4 agonists like HMGB1 or HSP70. Moreover, recently it has
emerged that ICD may also be associated with a "viral response-like chemokine signature
(VCS)" capable of acting as both 'find me' signal (for granulocytic myeloid cells) and 'keep
away' signal (for immature monocytic myeloid cells) - further details of this paradigm are
under investigation.
Thus, the presence of these molecular determinants of ICD can be used to monitor the host
immune status and as a predictive biomarker. Examples include: danger signals as surrogate
positive biomarkers (HMGB1, HSP70 and autoantibodies against CRT/HSP90); viral-response like
chemokine signature as direct positive biomarkers (IFN1A, IFN1B and CXCL10>CCL2>CXCL1).
The presence of determinants of ICD can be confirmed through the strategy of following
biomarkers (in non-hematological cancers):
- Cancer cell-associated pro-tumorigenic cytokines/factors IL1A, IL10, IL6, TGF-B, VEGFA,
VEFGC, IDO enzyme, CXCL12, IL8
- Immune cell-associated pro-tumorigenic cytokines/chemokines/factors IL10, IDO enzyme,
TGF-B, IL4, IL5, IL13, TNF, M-CSF, GM-CSF, IL26, CXCl5, CCL7
- danger signals as surrogate positive biomarkers HMGB1, HSP70 and autoantibodies against
CRT/HSP90
- Cancer cell-associated viral response-like chemokine signature IFN-a, IFN-b, CXCL9,
CXCL10, CXCL1 and CCL2
- Immune cell-associated anti-tumorigenic cytokines or chemokines as positive biomarkers
IL1B, IL12p70, IL15, IFNG, IL22, IL23, IL17A, IL2, CCL4, CCL5, CXCL13, CCL8, CCL19,
CXCL11,CCL12, CCL17, CCL23, CCL22, CCL13, CCL24, CCL1, CCL26, CXCL2, CXCL16 Moreover,
the investigators will also investigate serum-associated exosomes as possible biomarkers
of an efficient antitumor response. Compared to certain soluble biomarkers (which are
accessible and thus more susceptible to extracellular proteases), exosomal biomarkers
can exhibit a longer half-life than their soluble equivalents, due to the "protection"
provided by their encompassing lipid membrane. Therefore, the investigators are also
interested in exploiting exosomes as a source of antitumor response information and as
novel biomarkers of therapeutic success (those mentioned above and others under
investigation).
Radiotherapy has been established through various robust lines of in vitro and in vivo
evaluation to be capable of inducing ICD and anticancer immune responses. As an exploratory
analysis, we will integrate lipidomics into the workflow. This has already been done in
multiple disease settings and NSCLC has already proven to change lipid content in a
quantifiable manner. The aim of this pilot study is to investigate the hypothesis that
certain biomarkers of ICD that were identified in vitro or ex vivo are detectable in patient
sera following radiotherapy and/or chemotherapy. Radiotherapy alone or concurrent
cisplatin-doublet and radiotherapy will be investigated. The investigator will conduct this
pilot study to gather initial data to build upon in future clinical trials, as there is no in
vivo data available on this topic. Results will be published and used for future grant
applications.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05094804 -
A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents
|
Phase 1/Phase 2 | |
Recruiting |
NCT05707286 -
Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
|
||
Recruiting |
NCT04258137 -
Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study
|
N/A | |
Completed |
NCT01945021 -
Phase II Safety and Efficacy Study of Crizotinib in East Asian Patients With ROS1 Positive, ALK Negative Advanced NSCLC
|
Phase 2 | |
Completed |
NCT04487457 -
Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy
|
||
Terminated |
NCT04022876 -
A Study of ALRN-6924 for the Prevention of Chemotherapy-induced Side Effects (Chemoprotection)
|
Phase 1 | |
Recruiting |
NCT05898763 -
TEIPP Immunotherapy in Patients With NSCLC
|
Phase 1/Phase 2 | |
Recruiting |
NCT05532696 -
Phase 1b/2 Study to Evaluate ABT-101 in Solid Tumor and NSCLC Patients
|
Phase 1/Phase 2 | |
Completed |
NCT04311034 -
A Study of RC48-ADC in Subjects With Advanced Non-small Cell Lung Cancer
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT03177291 -
Pirfenidone Combined With Standard First-Line Chemotherapy in Advanced-Stage Lung NSCLC
|
Phase 1 | |
Terminated |
NCT03257722 -
Pembrolizumab + Idelalisib for Lung Cancer Study
|
Phase 1/Phase 2 | |
Completed |
NCT00349089 -
Trial on Refinement of Early Stage Lung Cancer Adjuvant Therapy
|
Phase 2 | |
Completed |
NCT05116891 -
A Phase 1/2 Study of CAN04 in Combination With Different Chemotherapy Regimens in Subjects With Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT04571632 -
Clinical Trial of SBRT and Systemic Pembrolizumab With or Without Avelumab/Ipilimumab+ Dendritic Cells in Solid Tumors
|
Phase 2 | |
Terminated |
NCT03599518 -
DS-1205c With Gefitinib for Metastatic or Unresectable Epidermal Growth Factor Receptor (EGFR)-Mutant Non-Small Cell Lung Cancer
|
Phase 1 | |
Not yet recruiting |
NCT06020989 -
Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy
|
Phase 2 | |
Withdrawn |
NCT03982134 -
PDR001 + Panobinostat for Melanoma and NSCLC
|
Phase 1 | |
Withdrawn |
NCT03574649 -
QUILT-2.024: Phase 2 Neoadjuvant, Consolidation, and Adjuvant Combination NANT Immunotherapy Versus Standard of Care in Subjects With Resectable Non-small Cell Lung Cancer
|
Phase 2 | |
Withdrawn |
NCT02844140 -
DE-CT in Lung Cancer Proton Therapy
|
N/A | |
Terminated |
NCT02628535 -
Safety Study of MGD009 in B7-H3-expressing Tumors
|
Phase 1 |